Excessive Zn2+ influx has been implicated in the pathogenesis of neuronal death after global ischemia or prolonged seizures, but little is presently known about cellular regulation of intracellular free Zn2+ ([Zn2+]i). In large part, this is because the tools currently available for measuring [Zn2+]i are limited in comparison to those available for measuring [Ca2+]i or other ions. We outline here approaches to this task that have been taken in the past, and summarize our recent experience using mag-fura-5 to measure [Zn2+]i in living cortical neurons exposed to toxic levels of extracellular Zn2+.